Dimethylformamide → HCID 178452358, compound

HRID 489934Notes

Reaction equation

HRID 489934 reaction equation
O.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:13][N:12]=[C:11](C(O)=O)[C:10]=2[C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[CH:5][CH:4]=1.ON1C2C=C[CH:31]=[CH:32][C:27]=2N=N1.C([O:37][C:38]([N:40]1[CH2:45]CNC[CH2:41]1)=[O:39])CCC.[CH3:46]N1CCOCC1.[CH3:53][N:54]([CH:56]=[O:57])[CH3:55]>C(OCC)(=O)C>[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:13][N:12]=[C:11]([C:56]([N:54]3[CH2:55][CH2:45][N:40]([C:38]([O:39][C:32]([CH3:31])([CH3:27])[CH3:46])=[O:37])[CH2:41][CH2:53]3)=[O:57])[C:10]=2[C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 21963126Butyl piperazine-1-carboxylateHCID 178526953HCID 178526953, compound

Product 1

HCID 178452358HCID 178452358, compoundYield 78.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazole-3-carboxylic acid, monohydrate prepared in accordance with Example A-200 (0.9905 g, 3.5 mmol) and 1-hydroxybenzotriazole (0.4824 g, 3.57 mmol) in DMF (20 ml) at 0° C. under nitrogen, 1-(3-dimethylaminopropyl) 3-ethylcarbodiiminde hydrochloride (0.6984 g, 3.57 mmol, Aldrich Chemical Co.) was added. The solution was stirred at 0° C. under nitrogen for 1 hour then 1-butoxycarbonylpiperazine (0.6585 g, 3.5 mmol) was added followed by N-methylmorpholine (0.40 ml, 3.6 mmol). The reaction was stirred from 0° C. to room temperature overnight. After 19 hours, the solvent was removed under reduced pressure, and resulting residue was diluted with ethyl acetate, washed with saturated NaHCO3 solution, water and brine, and dried over MgSO4. After filtration, the solvent was removed under reduced pressure to give a crude product (1.7595 g). 1,1-Dimethylethyl 4-[[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl]carbonyl]-1-piperazinecarboxylate (1.2372 g, 78.4%) was obtained by chromatography. Anal. Calc'd for C24H26N5O3F. (451): C, 63.85; H, 5.80; N, 15.51; Found: C, 63.75; H, 5.71; N, 15.16. MS (MH+) 452 (base peak)

Workup

  1. addition1-(3-dimethylaminopropyl) 3-ethylcarbodiiminde hydrochloride (0.6984 g, 3.57 mmol, Aldrich Chemical Co.) was added
  2. stirringThe reaction was stirred from 0° C. to room temperature overnight
  3. waitAfter 19 hours
  4. customthe solvent was removed under reduced pressure
  5. customresulting residue
  6. washwashed with saturated NaHCO3 solution, water and brine
  7. dry with materialdried over MgSO4
  8. filtrationAfter filtration
  9. customthe solvent was removed under reduced pressure
  10. customto give a crude product (1.7595 g)

Sources & evidence

ORD record
ord-01c09e6d3e034356b0d39e2b6debb5e8
Source dataset
uspto-grants-2005_12
Patent number
US06979686B1

Reaction notes

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